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1.
PurposeTRAPPC9 deficiency is an autosomal recessive disorder mainly associated with intellectual disability (ID), microcephaly, and obesity. Previously, TRAPPC9 deficiency has not been associated with biochemical abnormalities.MethodsExome sequencing was performed in 3 individuals with ID and dysmorphic features. N-Glycosylation analyses were performed in the patients’ blood samples to test for possible congenital disorder of glycosylation (CDG). TRAPPC9 gene, TRAPPC9 protein expression, and N-glycosylation markers were assessed in patient fibroblasts. Complementation with wild-type TRAPPC9 and immunofluorescence studies to assess TRAPPC9 expression and localization were performed. The metabolic consequences of TRAPPC9 deficiency were evaluated using tracer metabolomics.ResultsAll 3 patients carried biallelic missense variants in TRAPPC9 and presented with an N-glycosylation defect in blood, consistent with CDG type I. Extensive investigations in patient fibroblasts corroborated TRAPPC9 deficiency and an N-glycosylation defect. Tracer metabolomics revealed global metabolic changes with several affected glycosylation-related metabolites.ConclusionWe identified 3 TRAPPC9 deficient patients presenting with ID, dysmorphic features, and abnormal glycosylation. On the basis of our findings, we propose that TRAPPC9 deficiency could lead to a CDG (TRAPPC9-CDG). The finding of abnormal glycosylation in these patients is highly relevant for diagnosis, further elucidation of the pathophysiology, and management of the disease.  相似文献   
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Forgiveness has been found one substantial element in the recovery for women survivors from intimate partner violence following the termination of the abusive relationship. To further investigate the details of forgiveness in this specific context, the present study explored the process of forgiveness using grounded theory. In-depth and semi-structured interviews were conducted with 25 Chinese women survivors of IPV. The findings suggest that forgiveness is a strength-based process including empowerment, transformation, and integration phases. In the empowerment phase, survivors obtain strength at the intrapersonal, behavioural, and interpersonal levels. In the transformation phase, survivors complete cognitive transformation for their IPV experiences and emotional transformation towards former partners. In the integration phase, survivors—now freed from the past—reflect upon and apply the changes they have undergone. Two trajectories in the process were found. One trajectory is going through stages sequentially and the other trajectory is experiencing back and forth between empowerment and transformation stages before moving into the integration stage. The study's findings broaden our knowledge of the strength-based forgiveness process that women survivors of IPV undergo during recovery. Practitioners and policymakers could develop programmes and policies that support forgiveness by holistically facilitating their recovery and empowerment like assistance in dealing with life difficulties and promoting their reconnection with social networks. To improve the transferability and validity of the findings, the forgiveness of survivors of IPV could be explored in a diverse sample (e.g., survivors with low educational background or live in the rural area).  相似文献   
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Archives of Women's Mental Health - Limited research exists on suicidal behaviors among women with disabilities. This study examined disability, suicidal behaviors, and associated health...  相似文献   
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Journal of Public Health - Offshore wind energy is a fast growing market. Accordingly, a correspondingly large number of employees are working at the wind farms. Owing to the harsh operating...  相似文献   
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Breast Cancer Research and Treatment - To critically review available literature on hypofractionated (≥?3 Gy/fraction) proton therapy (PT) for breast cancer (BCa). A systematic...  相似文献   
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Circulating microRNAs (c-miRs) are small noncoding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.  相似文献   
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Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma, as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments. Jaundice, gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity, resulting in potentially deleterious chemotherapy discontinuation, whose resumption relies on effective, prompt and long-lasting management of these complications. Although therapeutic endoscopic ultrasound (t-EUS) can potentially offer some advantages over comparators, its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery. This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy, gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario. Proof-of-concept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery. Moreover, the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation, potentially resulting in higher subsequent resectability. Available evidence is discussed in this short paper, together with technical notes that might be useful for endoscopists and surgeons operating in this scenario. No published evidence supports restricting t-EUS in potential surgical candidates, especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy. Bridge-to-surgery t-EUS deserves further prospective evaluation.  相似文献   
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